Migraine is the most common neurological disorder, and affects over 10% of the population in any given year, with over half of these individuals reporting severe impairment. For many patients, a severe, even disabling, component of the migraine attack is photophobia, yet neuroscientists are just starting to investigate the underlying neurobiological mechanisms. The present application tests the overarching hypothesis that brainstem pain-modulating circuits, already implicated in migraine-related pain, also contribute to migraine-related photophobia. This hypothesis is based on the entirely unexpected observation that pain-modulating neurons in the rostral ventromedial medulla, the final output of an important brainstem pain-modulating system, develop photoresponsiveness in animal models of migraine headache, although they do not respond to light under normal conditions. In three Specific Aims using the nitroglycerin migraine model in the rat, we will document light-evoked activity in identified pain-modulating neurons and determine whether this is specific to migraine. We will also determine whether pain- modulating systems contribute to light aversion and light-induced pain enhancement. Finally, we will identify possible pathways through which light gains access to pain- modulating systems. The present proposal brings together electrophysiological and behavioral approaches to show how light engages pain-modulating systems to produce photophobia. These studies will provide insights into the neurobiological mechanisms of migraine-related photophobia, fundamental information critical for developing new migraine treatments.